Widest gene study shows complex scale of obesity

Paris (AFP) – The largest-ever DNA probe into obesity has thrown up scores of clues for the inherited factors behind a worsening health problem, researchers said on Wednesday.

Investigators said they netted more than 100 previously-undiscovered gene variants which play a part in obesity’s complex processes.

Some variants may explain why some individuals are more prone than others to dangerous patterns of fat deposit, they added.

The work, by an international team called the Genetic Investigation of Anthropometric Traits (GIANT) consortium, entailed matching the genomes of half a million people against their measurements for body fat in order to tease out telltale signatures.

In one probe, the scientists found 49 such variations, 33 of which had not been previously spotted, that correspond to an obesity benchmark called the waist-to-hip circumference ratio.

A woman holds a large soda on a street in New York, USA, May 31, 2012. The largest-ever DNA probe into obesity has thrown up scores of clues for the inherited factors behind a worsening health problem. EPA

People whose waistlines are larger than their hip circumference have relatively more fat surrounding the abdominal organs.

This makes them more at risk from diabetes and cardiovascular problems compared to people whose fat is concentrated more in the hips or distributed equally around their body.

“We need to know these genetic locations because different fat depots pose different health risks,” said Karen Mohlke, a professor at the University of North Carolina School of Medicine who led the probe.

The team also found 19 genetic locations among women with a bigger waist-to-hip ratio – a finding that could help to explain why patterns of obesity can affect genders differently.

In the second paper, also published in the journal Nature, a team found 97 regions on the genome, 56 of which were new, that influence obesity in some way.

Many of these sites are found in genes involved in brain signalling, controlling appetite and use of energy.

Parts of the world are in the grip of an obesity epidemic, driving up incidence of diabetes, heart attacks and strokes.

According to the UN’s World Health Organization (WHO), obesity nearly doubled worldwide from 1980 to 2008.

More than 2.8 million adults die each year as a result of being overweight or obese, it says. A full 42 million children under the age of five are considered to be obese.

Diet and a sedentary lifestyle have long been fingered as causes of obesity, but in recent years, advances in gene sequencing have turned attention to inheritance.

Previous studies have variously estimated genes as being to blame for between 40 and 70 per cent of the problem.

Genomics could provide a diagnostic tool, helping to provide lifestyle advice to people who are genetically more at risk of obesity than others.

Ultimately, researchers hope, it could lead to new treatments to block or brake the molecular machinery which causes obesity.

The new haul of genetic variants may be part of a much larger final tally.

“Our work clearly shows that predisposition to obesity and increased BMI (body mass index, a measure of fat) is not due to a single gene or genetic change,” said Elizabeth Speliotes, a special in computational medicine at the University of Michigan.

“The large number of genes makes it less likely that one solution to beat obesity will work for everyone.”

But, she said, it also “opens the door to possible ways we could use genetic clues to defeat obesity.”